Secondary Conditions After SCI: Recognizing and Treating Cardiovascular Disease, Osteoporosis and Bl

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Secondary Conditions After SCI Recognizing and
Treating Cardiovascular Disease, Osteoporosis and
Bladder Cancer

• Suzanne L. Groah, MD, MSPH
• www.SCI-Health.Org

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Objectives

• List 3 major secondary conditions that occur
  after SCI
• Discuss risk factors for each of these secondary
  conditions
• Describe when and how to monitor for these
  secondary conditions

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Part 1 Bladder Cancer Risk and Prevention
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Bladder Cancer Epidemiology

• 5th most common cancer
• 12th leading cause of cancer mortality
• Adjusted yearly incidence 17.0 per 100,000
• 54,400 new cases per year
• Males at greater risk
• Majority are transitional cell carcinoma

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Risk Factors for Bladder Cancer

• Smoking
• Male gender
• Aromatic amines
• Schistosomiasis
• UTI

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Hypotheses

• Incidence of bladder cancer is higher in SCI than
  in the general population
• Indwelling catheter use is associated with
  bladder cancer in SCI
• 3 There is an increasing risk of bladder cancer
  with longer duration of IDC use

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Part 1 Design Retrospective Cohort
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Results
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Demographics
data presented in years
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Demographics
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Comparison to General Population (SMRMales)
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Risk of Bladder Cancer

• Age-adjusted rate of bladder cancer (per 100,000)
• Indwelling catheter - 77.0
• Multi methods- 56.1
• No indwelling catheter - 25.1
• Age-adjusted RR 4.9
• Attributable risk percent due to catheter 64.8
• Attributable risk percent due to SCI 55.8

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Factors Contributing to Bladder Cancer
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Cumulative Incidence of Bladder Cancer
Wilcoxan lt 0.05
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Cumulative Incidence of Bladder Cancer
Wilcoxan lt 0.05
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Part 1 Conclusions

• Incidence of bladder cancer is higher in SCI than
  in the general population
• Indwelling catheter use is associated with
  bladder cancer in SCI
• The risk of bladder cancer increases with
  increasing duration of indwelling catheter use

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Part 2 Bladder Cancer Mortality
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Epidemiology of Bladder Cancer Mortality

• Adjusted risk 3.2 per 100,000
• Associated with age
• gt50 deaths occur in 70 year olds
• Mortality related to stage at diagnosis
• Superficial 5-yr survival 90
• Invasive 5-yr survival lt50

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Hypotheses

• Bladder cancer mortality is heightened in SCI
  compared with the general population
• 2 Compared with other bladder management methods,
  indwelling catheter use is associated with
  heightened BC mortality
• 3 The risk of BC mortality increases with
  increasing duration of indwelling catheter use

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Part 2 Design Retrospective Cohort
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Bladder Cancer Mortality
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Risks

• Indwelling catheter age-adjusted BC mortality
  51.2/100,000 p-y
• Multi age-adjusted BC mortality 31.5/100,000
  p-y
• SMR SCI vs. SEER 70.9
• SMR IDC vs. SEER 127.9

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Bladder Cancer Mortality by Age
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Proportional Mortality Due to Bladder Cancer
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Survival After Bladder Cancer Diagnosis

• Of those dying due to BC, majority of death
  occurred in lt1 year
• Survival range .4 3.3 years

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Part 2 Conclusions

• Bladder cancer mortality is heightened in SCI
  compared with the general population
• Compared with other bladder management methods,
  IDC use is associated with heightened BC
  mortality

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Part 3 Risk Factors, Diagnosis, and Surveillance
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Purpose

• To evaluate factors influencing survival after
  bladder cancer in individuals with SCI
• To examine bladder cancer surveillance

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Hypotheses

• Bladder cancer survivors have fewer genitourinary
  risk factors than those dying due to bladder
  cancer
• 2 Bladder cancer survivors have undergone more
  intense genitourinary surveillance

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Part 3 Design Case-control
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Methods

• Design case-control
• 8 BC survivors
• 12 BC controls who died
• Outcome measures
• Demographics
• Frequency of surveillance
• Risk factors
• Analyses
• Students t test
• Fishers exact test

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Demographics
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Demographics
data presented in years
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Presentation
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Diagnosis
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Bladder Cancer Histology
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Potential Associated Risk Factors
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Risk Factors
RF IDC use, tobacco use, calculi, or
pyelonephritis
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Hypothesis 2

• 2 Bladder cancer survivors have undergone more
  intense genitourinary surveillance

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Bladder Cancer Surveillance
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Conclusions

• Bladder cancer survivors have fewer genitourinary
  risk factors than those dying due to bladder
  cancer
• While IDC use is related to BC incidence,
  concurrent multiple risk factor status may be
  related to mortality
• Bladder cancer survivors have undergone more
  intense genitourinary surveillance

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Clinical Correlates

• Encourage methods of bladder management other
  than indwelling catheters when appropriate
• Foley and suprapubic catheters DO have a role
  after SCI
• In people at risk, encourage periodic screening
  by a urologist

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Cardiovascular Disease
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Epidemiology of Cardiovascular Disease

• CVD is 1 cause of death in US
• 1993 CVD mortality rate 163 per 100,000
• 1993 CHD mortality rate 95 per 100,000
• 28.6 decline in mortality due to MI
• 84.6 of mortality due to MI in 65yo

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Reversible Risk Factors for CVD

• Hypertension
• Low HDL cholesterol
• Hypercholesterolemia
• Hypertriglyceridemia
• High lipoprotein A

• Tobacco use
• Sedentary lifestyle
• Abdominal obesity
• Diabetes mellitus
• Hyperinsulinemia

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Data from the Craig Collaborative Aging Study
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Cholesterol Level by Neurologic Group
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Serum Lipids

• Cholesterol significantly higher in ParaABCs and
  All Ds than TetraABCs
• HDL significantly lower in TetraABCs than All
  Ds
• HDL decreased significantly in ParaABCs and
  TetraABCs over time

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CVD and CHD Mortality

• 33 total deaths
• CVD mortality rate 42
• CHD mortality rate 33
• CVD case fatality rate 22
• CHD case fatality rate 17

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Epidemiology of CHD and CVD

• General population
• CVD 1 COD
• CHD prevalence 12.7-22
• CHD accounts for 51.2 of CVD mortality
• 17 CVD mortality in lt65 yo

• Long-term SCI
• CVD 1 COD (30 yrs post-SCI)
• CHD prevalence 15
• CHD accounts for 79 of CVD mortality
• 64 CVD mortality in lt65 yo
• 35 deaths in those gt60 years

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Data from Cardiovascular Disease After Spinal
Cord Injury Suspected Causes, Available
Treatments, and Investigational Imperatives
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National Cholesterol Education Panel Guidelines

• HDL lt 40 is abnormal
• LDL 130 159 is borderline high
• LDL gt 160 is high
• LDL target is 100
• Triglyceride 150-199 is borderline high
• Triglyceride lt 150 is normal

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Observed Lipid Levels After Chronic Paraplegia

• Normal total cholesterol
• Normal or elevated LDL
• Normal or elevated triglycerides
• Consistently low HDL
• Significantly elevated TCHDL ratio

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Data from the University of Miami Risk
Stratification of Young, Healthy, Tobacco
Non-Users with Paraplegia at T6 and Lower Using
NCEP Guidelines
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Lipid Abnormalities

• ATP X s.d. Min Max Risk At Risk
• TC (mg/dl) II 172 34 97 225 lt 200 10/46
• III lt 200 10/46
• TG (mg/dl) II 189 45 100 300 lt 200 14/46
• III lt 150 32/46
• TC/HDL-C 4.2 1.1 2.4 6.5 lt 4.5 21/46

data from M. Nash, University of Miami, Miami
Project to Cure Paralysis
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Lipid Abnormalities

• ATP Mean s.d. Min / Max Risk At Risk
• HDL-C (mg/dl) II 44 12 23 / 68 gt 35
  14/46
• III gt 40 25/46
• LDL-C (mg/dl) II 90 26 40 / 139 lt
  130/160 16/46 1
• III lt 100/130 32/46 2
• ?2 (1) 70.453, p lt 0.001
• 1 ATP II Lipid-Lowering intervention indicated
  in 16/46 (34.7) cases
• 2 ATP III Lipid-Lowering intervention indicated
  in 20/26 (69.6) cases

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Etiology of Lipid Abnormalities After Paraplegia

• Sedentary Lifestyle / Physical Deconditioning (L)
• Insulin Resistance / Metabolic Syndrome (X) (L,P)
• Imprudent Diet (P?)

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Clinical Correlates

• Role of nutrition and exercise
• Exercise may not be enough to correct the lipid
  abnormalities associated with SCI
• Monitor cholesterol and lipid levels
• Screen with exercise stress test

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Abnormal Calcium and Bone Metabolism After SCI
Osteoporosis, Stones and More
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Osteoporosis

• SCI results in immediate and often permanent
  gravitational unloading
• Similar to space flight
• Bone loss is universal after SCI
• Most persons with SCI will have a pathologic
  fracture at some point
• Osteoporosis occurs rapidly

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Bone Metabolism

• Normally there is a balance between
• Osteoclast (bone resorption/breakdown) activty
• Osteoblast (bone rebuilding) activity
• Pathology after SCI
• Imbalance between bone breakdown and bone
  formation
• After SCI osteoblastic AND osteoclastic activity
  increase
• Osteoblasts increase only slightly
• Osteoclast activity increases 10-fold, peaking at
  10 weeks

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Etiology of Osteoporosis After SCI

• Gravitational unloading
• Lack of muscle traction on bone
• Acutely, absorption of Ca decreases after SCI
• Other neural factors

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Pathology of Abnormal Bone and Calcium Metabolism

• Increase in osteoclast activity within days/weeks
• ? urine calcium
• Observed within 10d, peaks 1-6m
• 2-4x that seen in people after prolonged bedrest
• ? blood calcium
• ? markers of bone resorption

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Osteoporosis

• Definition - Bone density less than 2.5 SD below
  mean
• Bone density loss
• Trabecular bone affected most
• Distal femur
• Proximal tibia
• Os calcis
• Bone loss greater with
• Paraplegics have gt arm BMD than tetraplegics
• Complete injury

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Bone Loss or Gain Post-SCI
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Osteoporosis

• Morbidity
• Pathologic fracture in 6
• Outpatient Model System Center review
• 14 at 5 years
• 28 at 10 years
• 39 at 15 years
• Sites
• Supracondylar region and tibia
• ? Fracture threshold of 50 loss for the knee
• Inciting event minimal/no trauma, ROM

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Osteoporosis

• Prevention
• Exercise
• Medications
• Restoration of bone loss difficult
• Monitor at risk individuals

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Osteoporosis/Abnormal Bone Metabolism

• Exercise
• Animal model Early mobilization of paralyzed
  limbs with FES slowed bone loss
• Acute (1-4 week) standing program slowed bone
  loss at the tibia
• Acute (1-5 weeks) standing/treadmill program in
  incompletes halted bone loss
• FES ambulation in completes with chronic SCI did
  not restore BMD loss
• FES cycling does not restore BMD chronically

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Osteoporosis/Abnormal Bone Metabolism

• Exercise
• FES to quads 1 hr/d, 5 d/wk x 24 weeks restores
  LE bone loss (Belanger)
• FES-cycle 30min/d, 3d/wk x 12 mos restores 10
  proximal tibia bone loss (Mohr)
• FES-cycle 30min/d, 1d/wk x 12 mos did not change
  proximal tibia bone loss
• RRTC Project R2 effect of FES 1hr/d, 5d/wk x 6
  weeks acutely

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Osteoporosis/Abnormal Bone Metabolism

• Pharmacologic
• Bisphosphonates
• Etidronate shown to prevent BMD loss acutely,
  but may inhibit formation
• Pamidronate IV inhibited bone resorption and
  reversed PTH inhibition
• Alendronate increase BMD in ASIA D
• Zoledronate

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Clinical Correlates

• Osteoporosis is universal after SCI
• Osteoporosis likely can be prevented, but to what
  degree and for how long?
• Consider assessing BMD before initiating standing
  or especially ambulation program
• Consider assessment of BMD in those with chronic
  SCI

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Thank you